973 resultados para DNA damage response


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The objective was to investigate the influence of age on sperm DNA damage. Semen samples were collected from 508 men in an unselected group of couples attending infertility investigation and treatment. DNA fragmentation in spermatozoa was measured by TdT (terminal deoxynucleotidyl transferase)-mediated dUTP nick-end labelling (TUNEL) assay; at least 200 spermatozoa in randomly selected areas of microscope slides were evaluated using a fluorescent microscope and the percentage of TUNEL positive spermatozoa was determined. The number of cells with red fluorescence (TUNEL positive) was expressed as a percentage of the total sample [DNA fragmentation index (DFI)]. Age was treated as a continuous variable for regression and correlation analysis. The following male age groups were used: Group I: â¤35 years, Group II: 36-39 years, and Group III: â¥40 years. DFI was significantly lower in Group I than in Group II (P = 0.034) or III (P = 0.022). There was no difference in DFI between Groups II and III. In addition, regression analysis demonstrated a significant increase in sperm DFI with age (P = 0.02). TUNEL assay clearly demonstrates an increase in sperm DNA damage with age. © 2007 Published by Reproductive Healthcare Ltd.

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4-Methylesculetin (4-ME) is a synthetic derivative of coumarin that displays a potent reactive oxygen species (ROS) scavenger and metal chelating agent and therefore has been produced to help reduce the risk of human disease. The main objective of this study was to investigate the in vivo genotoxicity of 4-ME and initially to verify its potential antigenotoxicity on doxorubicin (DXR)-induced DNA damage. Different doses of 4-ME (500, 1000 and 2000mgkg -1 body weight) were administered by gavage only or with a simultaneous intraperitoneal (i.p.) injection of DXR (80mgkg -1). The following endpoints were analyzed: DNA damage in peripheral blood, liver, bone marrow, brain and testicle cells according to an alkaline (pH>13) comet assay and micronucleus induction in bone marrow cells. Cytotoxicity was assessed by scoring polychromatic (PCE) and normochromatic (NCE) erythrocytes (PCE/NCE ratio). No differences were observed between the negative control and the groups treated with a 4-ME dose for any of the endpoints analyzed, indicating that it lacks genotoxic and cytotoxic effects. Moreover, 4-ME demonstrated protective effects against DXR-induced DNA damage at all tested doses and in all analyzed cell types, which ranged from 34.1% to 93.3% in the comet assay and 54.4% to 65.9% in the micronucleus test.

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PURPOSE:To investigate the effects of occupational exposure to waste anesthetic gases on genetic material and antioxidant status in professionals during their medical residency. METHODS:The study group consisted of 15 medical residents from Anesthesiology and Surgery areas, of both genders, mainly exposed to isoflurane and to a lesser degree to sevoflurane and nitrous oxide; the control group consisted of 15 young adults not exposed to anesthetics. Blood samples were drawn from professionals during medical residency (eight, 16 and 22 months of exposure to waste anesthetic gases). DNA damage was evaluated by comet assay, and antioxidant defense was assessed by total thiols and the enzymes glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT). RESULTS:When comparing the two groups, DNA damage was significantly increased at all time points evaluated in the exposed group; plasma thiols increased at 22 months of exposure and GPX was higher at 16 and 22 months of exposure. CONCLUSION:Young professionals exposed to waste anesthetic gases in operating rooms without adequate scavenging system have increased DNA damage and changes in redox status during medical residency. There is a need to minimize exposure to inhalation anesthetics and to provide better work conditions.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)